Since its inception in 1989, the Washington Heights and Inwood and Columbia Aging Project (WHICAP) has investigated rates and risk factors of Alzheimer's disease (AD) and related dementias in a multi-ethnic, urban community. In the previous five-year funding cycle, we made several key observations that have helped us to frame this new proposal. We found that elevated levels of plasma Abeta42 were associated with incident AD, that memory performance in elderly without dementia declines over time in those who with an ApoE4 allele compared with other APOE genotypes and that memory performance can be directly related to decreased basal metabolism in the hippocampus measured by magnetic resonance imaging (MRI). We established the first estimates of the prevalence and incidence rates of mild cognitive impairment (MCI) among elderly African-Americans and Caribbean Hispanics, comparing these estimates to the frequency of MCI in Caucasians. We found that rates of AD were higher among individuals following stroke and those with high insulin levels. We also observed found that mortality was increased by five-fold for individuals with newly diagnosed AD and that factors such as home health care extended survival and delayed nursing home admissions. In the previous cycle we also successfully recruited 2,103 individuals age 65 years and older, supplementing the survivors of the original cohort established in 1992. This new cohort, termed WHICAP II includes 2,767 individuals for which biological samples and clinical data are available from the baseline assessment. A Clinical Assessment Core, Epidemiology-Data Management-Statistical Core, Neuropathology and Molecular core are continued, and a Brain Imaging Core has been added to support five new projects. In addition to Alzheimer's disease (AD), this study will also examine mild cognitive impairment (MCI) as an outcome. In four of the five projects, we will include magnetic resonance imaging of brain. Each of the projects represents a direct extension from the work done in the previous 3 funding cycles. In Project 1 we will investigate plasma Abeta42 and both structural and function MRI as antecedent biomarkers in relation to the risk of MCI, AD and cognitive decline. In project 2, we will examine hyperinsulinemia, related cardiovascular and stroke as risk factors for MCI, AD and cognitive decline. Project 3 will continue to examine factors related to the progression of AD and its consequences. In Project 4, will examine parkinsonism as a risk factor for MCI and AD and examine imaging of basal ganglia. Project 5, will examine olfactory dysfunction as an antecedent risk factor for MCI and AD. The overall theme of this fourth renewal application is to identify reliable and valid antecedent biomarkers of AD and MCI and to extend these and other clinical parameters to the measurement of disease progression.